In vivo therapeutic effect of CDH3/P-cadherin-targeting radioimmunotherapy

Purpose

We examined the possible efficacy of the yttrium-90 (⁹⁰Y)-labeled anti-CDH3/P-cadherin mouse monoclonal antibody (MAb-6) in radioimmunotherapy (RIT) for lung and colorectal cancers that express CDH3/P-cadherin.

Experimental design

MAb-6 was established using genetic immunization. The biodistribution of MAb-6 in nude mice with lung and colorectal cancers was examined by administering indium-111(¹¹¹In)-labeled MAb-6 to mice. The mice were prepared by inoculation of CDH3/P-cadherin-positive (EBC1, H1373, and SW948) and CDH3/P-cadherin-negative (A549 and RKO) tumor cells. Therapeutic effects and toxicity were investigated by administration of ⁹⁰Y-labeled MAb-6 (⁹⁰Y-MAb-6) to EBC, H1373, and SW948-inoculated mice.

Results

Our in vivo results confirmed the specific binding of MAb-6 to tumor cells after intravenous injections of ¹¹¹In-labeled MAb-6 to mice with tumors expressing CDH3/P-cadherin. A single intravenous injection of ⁹⁰Y-MAb-6 (100?μCi) significantly suppressed tumor growth in mice with tumors expressing CDH3/P-cadherin. Furthermore, two injections of ⁹⁰Y-MAb-6 led to complete tumor regression in H1373-inoculated mice without any detectable toxicity.

Conclusions

Our findings demonstrate that CDH3/P-cadherin-targeting RIT with ⁹⁰Y-MAb-6 is a promising strategy for the treatment for cancers expressing CDH3/P-cadherin.